rs3821445

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000532.5(PCCB):c.654+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,475,928 control chromosomes in the GnomAD database, including 26,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2076 hom., cov: 32)

Exomes 𝑓: 0.19 ( 24303 hom. )

Consequence

PCCB
NM_000532.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.471

Publications

9 publications found

Variant links:

Genes affected

PCCB (HGNC:8654): (propionyl-CoA carboxylase subunit beta) The protein encoded by this gene is a subunit of the propionyl-CoA carboxylase (PCC) enzyme, which is involved in the catabolism of propionyl-CoA. PCC is a mitochondrial enzyme that probably acts as a dodecamer of six alpha subunits and six beta subunits. This gene encodes the beta subunit of PCC. Defects in this gene are a cause of propionic acidemia type II (PA-2). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

PCCB Gene-Disease associations (from GenCC):

propionic acidemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Myriad Women’s Health, Orphanet

PCCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-136283967-T-C is Benign according to our data. Variant chr3-136283967-T-C is described in ClinVar as Benign. ClinVar VariationId is 93231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PCCB	NM_000532.5 link	c.654+20T>C	intron_variant	Intron 6 of 14	ENST00000251654.9	NP_000523.2	P05166-1
PCCB	NM_001178014.2 link	c.714+20T>C	intron_variant	Intron 7 of 15		NP_001171485.1	P05166-2
PCCB	XM_011512873.2 link	c.654+20T>C	intron_variant	Intron 6 of 10		XP_011511175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9 link	c.654+20T>C		intron_variant	Intron 6 of 14	1	NM_000532.5	ENSP00000251654.4		P05166-1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23543

AN:

152072

Hom.:

2077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.00886

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.160

AC:

40117

AN:

250622

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.0986

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.00740

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.198

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.186

AC:

245783

AN:

1323738

Hom.:

24303

Cov.:

AF XY:

0.185

AC XY:

123148

AN XY:

666582

show subpopulations

African (AFR)

AF:

0.100

AC:

3093

AN:

30836

American (AMR)

AF:

0.152

AC:

6798

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

6570

AN:

25238

East Asian (EAS)

AF:

0.0147

AC:

576

AN:

39060

South Asian (SAS)

AF:

0.143

AC:

11922

AN:

83522

European-Finnish (FIN)

AF:

0.120

AC:

6342

AN:

52704

Middle Eastern (MID)

AF:

0.206

AC:

1041

AN:

5044

European-Non Finnish (NFE)

AF:

0.202

AC:

199262

AN:

987054

Other (OTH)

AF:

0.183

AC:

10179

AN:

55694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

9134

18267

27401

36534

45668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6506

13012

19518

26024

32530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.155

AC:

23546

AN:

152190

Hom.:

2076

Cov.:

AF XY:

0.152

AC XY:

11296

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.100

AC:

4157

AN:

41524

American (AMR)

AF:

0.176

AC:

2693

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

895

AN:

3472

East Asian (EAS)

AF:

0.00888

AC:

AN:

5178

South Asian (SAS)

AF:

0.141

AC:

678

AN:

4818

European-Finnish (FIN)

AF:

0.110

AC:

1167

AN:

10582

Middle Eastern (MID)

AF:

0.223

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.193

AC:

13137

AN:

68006

Other (OTH)

AF:

0.185

AC:

391

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

994

1989

2983

3978

4972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.193

Hom.:

3830

Bravo

AF:

0.159

Asia WGS

AF:

0.0820

AC:

288

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jun 11, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 04, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Propionic acidemia

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

(source)

DANN

Benign

0.58

PhyloP100

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over